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April 1997
Volume 61 |
Number 4
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| 'Fen/Phen' and
Anesthesia - Fact, Fiction and Other Concerns |
Asa C. Lockhart, M.D.
"Are Your Patients on Fen/Phen? You Had Better Get Them to
Tell You." Anecdotal reports point to cardiac arrest for
patients taking diet drug. - SAME-DAY SURGERY, January 1997.
"ASA is aware and
concerned about reports that some patients taking the diet drug
nicknamed "fen/phen," and not disclosing this to their
anesthesiologists prior to surgery, are experiencing adverse and
potentially deadly reactions while under general anesthesia."
- ASA Media Statement, October 1996.
If you think that "fen/phen" is not in your community,
you may just not be aware of it. "Fen/phen" is a combination
diet drug regime that combines fenfluramine with phentermine. There
is only one brand of fenfluramine (Pondimin) listed in the Physicians'
Desk Reference (PDR) while there are seven brands of phentermine
listed (Adipex, Fastin, Oby-Cap, Obenix, Oby-Trim, Zantryl and Ionamine.)
A stereo-isomer of fenfluramine has come onto the market only in
the past year (Redux).
Fenfluramine is a sympathomimetic amine that is pharmacologically
different from the usual amphetamine prototype; it tends to produce
more central nervous system (CNS) depression than stimulation.
Accordingly, it is combined with phentermine, a more classical
sympathomimetic amine, with CNS stimulating properties. The CNS
effects from the drug combination tend to cancel each other out
so that most patients primarily experience significant weight
loss without mood alteration.
There are several issues that need to be considered. Anecdotal
is a keyword. If speaking with the pharmaceutical representative,
one will most likely be informed that fen/phen does not exist.
The drugs have never been studied as a combination in an approved
Food and Drug Administration (FDA) protocol. We do not know if
there is a potentiation or summation of their individual actions,
some entirely new hybrid reaction, or no changes at all.
There are no scientific studies on the interaction with anesthetics
whether "fen/phen" components are taken individually
or in combination. It is important that the anesthesiologist is
informed by the patient of all medications, diet pills, vitamins
and herbal preparations. Except for the monoamine oxidase (MAO)
inhibitors, the only other listing involving anesthesia by name,
to this author's knowledge, occurs with fenfluramine.
The PDR contains a single paragraph relating to anesthesia and
fenfluramine under contraindications as follows:
"A fatal cardiac arrest has been reported shortly after
the induction of anesthesia in a patient who had been taking fenfluramine
prior to surgery. Fenfluramine may have a catecholamine-depleting
effect when administered for prolonged periods of time; therefore,
potent anesthetic agents should be administered with caution to
patients taking fenfluramine. If general anesthesia cannot be
avoided, full cardiac monitoring and facilities for instant resuscitative
measures are a minimum necessity."
At the time this drug met FDA approval, there were no monitoring
standards in place. This author is unsure of the approval date;
however, one case of cardiac arrest possibly related to fenfluramine
was reported in England in 1977. [1]
It involved a young patient undergoing a dental procedure with
halothane. Autopsy did not reveal any congenital or other obvious
predisposing abnormalities. Of course, there were many possible
causes. It was not felt at the time that it represented a halothane/epinephrine
sensitization type of reaction. Pulse oximetry and end-tidal CO2
were not readily available then. There was no mention of airway
problems.
While it is true that only one case was officially reported,
concern is with the phrase, "If general anesthesia cannot
be avoided, ..." When clarification was originally sought
from the manufacturer, the interpretation was that the phrase
meant to defer anesthesia and therefore surgery. The case that
spawned the initial inquiry into the subject was a carpal tunnel
release, which the author had planned to do under a Bier Block.
The company representative was not able to condone even that technique.
The company was trying to help with information, and the hesitation
was more related to FDA considerations and limitations.
While history has proven that earlier recommendations to discontinue
medications ranging from reserpine to propranolol to calcium channel
blockers were later shown to be unjustified, fenfluramine is different.
None of the other medications currently carries a written warning,
especially under contraindications, with relation to general anesthesia.
Fenfluramine shares this distinction with some MAO- inhibitors,
although many now feel that the key is to avoid Demerol while
others would not discontinue MAO-B but would discontinue MAO-A
class medications. The comfort level and the subsequent approaches
will vary with the practitioner.
If the decision is to defer surgery, how long should that be?
The half-life of fenfluramine is about 20 hours. The drug is eliminated
in approximately five half-lives, or about four days. Allowing
for individual variability, the delay should be about a week.
This is the basis for the recommendation to defer elective surgery
for one week. If, however, there is significant dopamine depletion,
time is needed for those stores to replete. Thus, this is the
empirical basis for the recommendations that suggest discontinuing
the drug for two weeks prior to elective surgery; this is the
most conservative approach.
It is important to note that there is no "standard"
and no one suggests deferring urgent procedures. One cannot
say that two weeks is better; it is just more conservative in
the absence of any scientific facts. Anecdotal is once again the
keyword, albeit an unfortunate one.
The following are concerns that we as anesthesiologists may wish
to consider:
- What is the real risk, if any, of clinically significant interaction
of fen/phen with anesthesia? Is there any risk with regional
anesthesia or monitored anesthesia care techniques?
- What is the liability of ignoring a contraindication, not
just a precaution, that has been published in the PDR? Could
this be construed in the context and era of "junk science"
to establish a pattern of negligence?
- Are there informed consent issues? What if patients have a
problem and claim, however remotely related, that had they been
informed of this risk, they would not have proceeded with an
elective procedure?
- Is there a mechanism for any entity affiliated with ASA (e.g.,
Anesthesia Patient Safety Foundation) to be the repository of
case reports in the absence of scientific consensus? Personally,
the author believes this is necessary in view of the anecdotal
reports; the alternative would be a scientifically valid study
to settle the issue. One cannot summarily dismiss anecdotal
reports. Patients should not be exposed to any unnecessary risks.
- following is the author's approach to the current concerns
with fen/phen:
- Our surgical offices were informed by the risk managers of
the hospital, and they are the initial screen. This has been
well-received in our medical community. With proper screening,
there is just a one-time potential delay of scheduled cases.
- Adult patients are specifically asked about fen/phen use in
our preoperative clinic - regardless of their weight. We have
had patients on these drugs who weighed approximately 100 pounds
and felt like they needed to "lose just a little."
- Inquiries can be made in the holding area; however, at this
stage, the patient is inconvenienced and has generated patient
charges. Yet until the first two screens are in place, this
is an essential element.
In summary, the risks of fen/phen and anesthesia are unknown.
There are anecdotal risks to the patient and potential liability
risks to the anesthesiologist. Our wish should be not to increase
the risk of either one but rather for both to be studied and settled
properly. Our overriding mission is to be the patient's advocate.
Editor's Note: ASA's media statement noted at the begining
of this article was prepared last October for CNN in lieu of an
interview with then ASA President Norig Ellison, M.D. It was not
then and is not now an official "standard of care" statement
by the ASA House of Delegates. Furthermore, it should be noted
that ASA is not commenting on the efficacy of fen/phen or its
use as a diet drug. Rather, ASA is more concerned that patients
who are having elective surgery make this information known to
their anesthesiologists during their medical history-taking.
Reference:
1. Bennett JA, Eltringham RJ. Possible dangers
of anaesthesia in patients receiving fenfluramine. Results of
animal studies following a case of human cardiac arrest. Anaesthesia.
1977; 32(1):8-13.
Asa C. Lockhart, M.D., is an attending
staff anesthesiologist at East Texas Medical Center Hospital and
Trinity Mother Frances Hospital, Tyler, Texas. He also is past
president of the Texas Society of Anesthesiologists.
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